Purpose: To evaluate the relationship between ocular discomfort and pterygium clinical characteristics.
Methods: The Ocular Comfort Index test was self-completed by 25 men and 15 women (age [mean ± SD], 43 ± 11 years) with primary pterygium. Pterygium corneal area (PCA) and limbal perimeter, course and bilaterality of the lesion, visibility of episcleral vessels, conjunctival hyperemia, and exposure to dry or dusty environments were assessed. Spearman correlation and multiple linear regression were performed to evaluate the relationship between ocular discomfort and pterygium clinical characteristics.
Results: Ocular discomfort was inversely correlated with PCA (ρ = −0.447, p < 0.01) and directly correlated with the exposure to dry or dusty environments (ρ = 0.324, p < 0.05). The other studied factors did not show any significant relationship with discomfort symptoms. The linear regression analysis identified PCA as the only factor that significantly influenced ocular discomfort (R = −0.404, p < 0.01).
Conclusions: The findings confirm an inverse linear relationship between ocular discomfort and PCA, providing evidence of corneal sensitivity loss in these patients.
Ocular Surface Research Group, Optics and Optometry Department, Universitat Politècnica de Catalunya, Terrassa, Spain (GJ, SL, PP, DM); and Department of Ophthalmology, Terrassa Hospital, Terrassa Health Consortium, Terrassa, Spain (PP).
Gemma Julio Universitat Politècnica de Catalunya Violinista Vellsolà 37 08222 Terrassa, BarcelonaSpain e-mail: firstname.lastname@example.org
Pterygium is a common ocular surface disease1,2 characterized by the encroachment of a fleshy fibrovascular formation from the bulbar conjunctiva across the limbus, invading the cornea. Theories of the pathogenesis of pterygium have implicated UV light exposure as a major causative factor.3–5 Other related factors are chronic eye inflammation; irritable reaction to wind, dust, smoke, and air pollution; and viruses.6 Excessive exposure to UVB could damage limbal stem cells, leading to aberrant wound healing responses.7 This triangular or wing-shaped lesion mainly grows along the nasal interpalpebral fissure and is often associated with inflammation, astigmatism, obstructed vision, and an unfavorable cosmetic effect.8 Clinical decisions about pterygium management are often influenced by morphological aspects of the lesion because they are considered markers of severity.9,10 In fact, a morphological classification based on the visibility of the underlying episcleral blood vessels is currently used to grade pterygia.11
Consensual indications for pterygium surgery include ocular surface discomfort, loss of visual acuity, increasing astigmatism, and impending invasion of the optical axis. Despite being a determining factor for surgery, ocular discomfort from pterygium has been poorly studied9,12 in contrast to other prevalent ocular surface diseases, such as dry eye disease. Many published works have measured the relationship between symptoms and signs in dry eye disease, with conflicting results.13,14 Similarly, the relation between pterygium and tear film function has been difficult to define. Some, but not all, findings from published studies have shown abnormal tear test results in these patients.15,16 Nevertheless, an unquestionable common feature of several ocular surface diseases, including pterygium, is chronic ocular inflammation, which has been described as one of the causes of corneal nerve injury.17 Under these adverse conditions, it stands to reason that trophic support to the corneal epithelium, as well as tissue sensitivity, could be diminished.
The aim of this study was to evaluate the relationship between ocular discomfort and pterygium clinical characteristics and thus provide evidence of conditioning clinical factors for ocular discomfort and an indirect approach to assessing corneal sensitivity.
Twenty-five men and 15 women with primary pterygium aged between 22 and 75 years (age [mean ± SD], 43 ± 11 years) were enrolled in the study. Patients with ocular allergy, infectious conjunctivitis, or surface ocular diseases other than pterygium were excluded. Subjects were recruited from Terrassa Hospital, and written informed consent was obtained from all of them. The clinical protocol and informed consent form were approved by the Terrassa Health Consortium Committee. The research followed the tenets of the Declaration of Helsinki.
The Ocular Comfort Index (OCI) was the symptom questionnaire chosen to measure the severity of ocular discomfort in the patients. The OCI, designed by Johnson and Murphy18 in 2007, has shown favorable psychometric properties for assessing the impact severity of some ocular surface diseases on patients’ well-being. Its major benefit over existing instruments is that it produces estimations on a linear interval scale rather than ordinal ranks, and therefore, it is more useful for quantifying changes.
Following the procedure of Johnson and Murphy,18 questionnaire answers (Table 1) reported by each patient were entered in a computer program written in a commercial software (Excel; Microsoft, Redmond, WA). This program used Rasch analysis software that, through maximum-likelihood iterative procedures, scored a global result of individual ocular discomfort on a 0 to 100 scale.18 These global scores were used as data for ocular discomfort severity in the statistical analysis. (Copies of the OCI questionnaire and calculator are freely available online at http://www.iovs.org/cgi/content/full/48/10/4451/DC1 courtesy of Johnson and Murphy.)
Several aspects of pterygium morphology were analyzed. The grade of visibility of episcleral vessels and conjunctival hyperemia were assessed under biomicroscopy by a single masked observer. Thus, pterygia were classified as atrophic when episcleral vessels were clearly distinguished, fleshy when they were totally obscured, and intermediate when the vessels were distinguished with difficulty. Conjunctival hyperemia was evaluated according to a grading scale with three grades: no or low hyperemia, mild hyperemia, and high hyperemia. Data about the course (1 to 5 years, 5 to 10 years, and >10 years) and bilaterality of the lesion, as well as exposure to dry or dusty environments (occasionally, some times a week, and daily), were also recorded in a questionnaire form. In addition, the pterygium corneal area (PCA) was quantified. The affected eye of each patient was photographed with a digital camera; in case of bilateral lesions, one of the two eyes was randomly chosen. The area within the corneal outline demarcation of the lesion was measured, in a semiautomatic way, by the Analyze/Measure command of ImageJ analysis software (W Rasband, National Institutes of Health, Bethesda, MD; http://rsb.info.nih.gov/ij/) using the polygon selection tool (Fig. 1). A ruler was used as the scale bar in the image for converting the squared pixels calculated by the program into square millimeters. We called this measure “pterygium corneal area.” Besides, the limbal perimeter affected by the lesion was also measured using the straight line selection tool, demarcating it segment by segment (Fig. 1). The measure was called “pterygium limbal perimeter.”
After an exploratory data analysis, the variables were tested for normality using the Kolmogorov-Smirnov test (p > 0.05). The linear relationship between the OCI global scores and the pterygium clinical characteristics, as well as the exposure to dry or dusty environments, was assessed by Spearman correlation.
Furthermore, a stepwise multiple linear regression analysis (inclusion and exclusion criteria determined by p < 0.05 and p > 0.10, respectively) was performed to evaluate the relationship between the OCI global scores and all the other studied variables (age, sex, visibility of episcleral vessels, conjunctival hyperemia, course and bilaterality of the lesion, exposure to dry or dusty environments, PCA, and limbal perimeter affected). All statistical analyses were performed using SPSS V19 (IBM SPSS Statistics; http://www-01.ibm.com/software/analytics/spss/). A value of p ≤ 0.05 or less was considered to denote statistical significance throughout the study.
The summary statistics of the OCI global scores and the other continuous variables are shown in Table 2. The pterygium patients displayed mild to moderate scores for ocular discomfort on the 0 to 100 test scale range, with most of the PCAs smaller than 10 mm2 and an affected limbal perimeter less than 6.5 mm. Distribution of the OCI answers (Table 3) is similar for all the items (ocular discomfort symptoms). The grade zero of frequency and severity included most of the responses and, as the grade increases, the number of answers progressively decreases. This pattern was extreme for “ocular pain” and “dryness” that showed the highest number of answers in the grade zero. Hence, they were considered the least reported symptoms. The exception to this general pattern was the item “itching” that showed a quite uniform number of answers in all the grades of frequency and severity.
Regarding clinical characteristics, pterygia were classified as atrophic in 12 patients (30%), fleshy in 10 patients (25%), and intermediate in 18 patients (45%). Bilateral lesion was present in 21 patients (52.5%), and conjunctival hyperemia was high in 13 patients (32.5%) and intermediate in 15 (37.5%), whereas 12 (30%) showed a white conjunctiva. Exposure to dry or dusty environments was occasional in 16 patients (40%), some times per week in 6 patients (15%), and daily in 18 patients (45%). Distribution of pterygium duration (Fig. 2) showed that 65% of the patients had the disorder for longer than 5 years.
The OCI global scores were significantly correlated with PCA (ρ = −0.447, p < 0.01). As the coefficient is negative, the higher the lesion size, the lower the ocular discomfort. In addition, OCI global scores significantly correlated with exposure to dry or dusty environments (ρ = 0.324, p < 0.05). Therefore, the more frequent the exposure to these adverse environments, the higher the ocular discomfort.
The stepwise multiple linear regression analysis identified PCA as the only explanatory variable significantly related to the ocular discomfort reported by the patients (R = −0.404, p < 0.01). Thus, the resulting equation was OCI = 41.559 − 1.427 * PCA.
The findings showed a significant inverse linear relationship between symptoms of ocular discomfort and PCA. This association seems to be confirmed because multivariate linear regression included lesion size as the only predictive variable of ocular discomfort. A direct linear relationship was also found between ocular discomfort symptoms and exposure to dry or dusty environments, but this variable was not included in the regression model; that is, it seems not to provide new information for improving the model. No other pterygium clinical characteristics (including clinical manifestation of inflammation) seem to be linearly related to ocular discomfort.
In a healthy eye, minor insults to the ocular surface heal rapidly within a continuous trophic environment created by the corneal nerves and tear film.19,20 Conscious sensations and reflex motor and autonomic responses aim at protecting the eye from further injury. However, this protective mechanism seems to fail when chronic inflammation accompanies an ocular disease17 and a reduction in corneal sensitivity has been reported, for instance, in dry eye disease,21,22 contact lens wearers,23 Graves orbitopathy,24 or herpes simplex virus keratitis.25 Chronic inflammation is also a common feature in pterygium, therefore, corneal hypoesthesia could be a plausible explanation for the paradoxical situation generated by the inverse correlation found between PCA and ocular symptoms.
In addition, the main etiopathological changes in pterygium are related to corneal subepithelial, Bowman, and basal epithelial layers7,26 between which the corneal nerve plexuses are located.27,28 It stands to reason that pterygium may cause some alterations in epithelial nerve terminals, modifying corneal sensitivity, especially with nerves penetrating radially from the limbus and the density of subepithelial plexus penetration being greater peripherally than centrally.29 In fact, morphologic alterations (higher tortuosity and number of vesicles) of the subbasal nerve plexus have been observed30,31 by confocal microscopy in the clear central cornea adjacent to the pterygium. Unfortunately, a corneal esthesiometer was not available at the study site. To our knowledge, only Stapleton and coworkers32 have published a study on direct assessment of corneal sensitivity under pterygium conditions. They found reduced sensations in a sample of 10 patients, a finding that supports our hypothesis. Nevertheless, further assessments with large samples will be required to confirm corneal sensitivity loss in this ocular pathology.
The results of our study displayed ocular pain sensation as the least reported symptom, possibly signaled by mechano and polimodal nociceptors, followed by dryness sensation that seems to be evoked, in part, through cold thermoreceptors.33 At least, these receptors might be damaged in pterygium patients. Chui and coworkers34 found upregulated immunoreactivity for receptors of the sensory neuropeptide substance P in pterygia and postulated that substance P may contribute to the shape of the lesion through its profibrogenic and angiogenic actions. The large number of transducing and receptor membrane proteins that have been linked with ocular inflammation or nerve damage in recent years35 suggests that corneal sensitivity changes under pterygium conditions are highly complex. In clinical practice, decreased nerve sensitivity clearly contributes to the lack of agreement between symptoms and signs—a frequent finding in dry eye disease.21,36 Similarly, a previously proposed pterygium activity score9,10 for assessing ocular discomfort among other clinical characteristics could, according to our results, generate uneven results.
In conclusion, ocular discomfort in pterygium patients seems to be inversely correlated with the corneal lesion size. This paradoxical situation could be caused by hypothetical, but plausible, corneal nerve damage. These findings advocate for exploring possible corneal hypoesthesia in patients with pterygium. Further assessments are required to confirm loss of sensitivity and to determine if it is caused by nerve damage, intrinsic to the proliferative disorder, or results from the chronic inflammation associated with pterygia.
Universitat Politècnica de Catalunya
Violinista Vellsolà 37
08222 Terrassa, Barcelona
The authors declare no conflicts of interest.
Part of this work has previously been presented as a poster at the XX Biennial Meeting of the International Society for Eye Research, July 21–25, 2012, in Berlin, Germany.
Received September 25, 2012; accepted November 14, 2012.
1. Gazzard G, Saw SM, Farook M, Koh D, Widjaja D, Chia SE, Hong CY, Tan DT. Pterygium in Indonesia: prevalence, severity and risk factors. Br J Ophthalmol 2002; 86: 1341–6.
2. Viso E, Gude F, Rodriguez-Ares MT. Prevalence of pinguecula and pterygium in a general population in Spain. Eye (Lond) 2011; 25: 350–7.
3. Coroneo MT. Pterygium as an early indicator of ultraviolet insolation: a hypothesis. Br J Ophthalmol 1993; 77: 734–9.
4. Di Girolamo N. Signalling pathways activated by ultraviolet radiation: role in ocular and cutaneous health. Curr Pharm Des 2010; 16: 1358–75.
5. Young RW. The family of sunlight-related eye diseases. Optom Vis Sci 1994; 71: 125–44.
6. Saw SM, Banerjee K, Tan D. Risk factors for the development of pterygium in Singapore: a hospital-based case-control study. Acta Ophthalmol Scand 2000; 78: 216–20.
7. Di Girolamo N, Chui J, Coroneo MT, Wakefield D. Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases. Prog Retin Eye Res 2004; 23: 195–228.
8. Chui J, Coroneo MT, Tat LT, Crouch R, Wakefield D, Di Girolamo N. Ophthalmic pterygium: a stem cell disorder with premalignant features. Am J Pathol 2011; 178: 817–27.
9. Labbé A, Gheck L, Iordanidou V, Mehanna C, Brignole-Baudouin F, Baudouin C. An in vivo
confocal microscopy and impression cytology evaluation of pterygium activity. Cornea 2010; 29: 392–9.
10. Twelker JD, Bailey IL, Mannis MJ, Satariano WA. Evaluating pterygium severity: a survey of corneal specialists. Cornea 2000; 19: 292–6.
11. Tan DT, Chee SP, Dear KB, Lim AS. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol 1997; 115: 1235–40.
12. Wilson G, Horner D, Begley C, Page J. Ocular discomfort from pterygium in men and women. Eye Contact Lens 2008; 34: 201–6.
13. Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and symptoms in patients with dry eye disease. Cornea 2004; 23: 762–70.
14. Julio G, Lluch S, Cardona G, Fornieles A, Merindano D. Item by item analysis strategy of the relationship between symptoms and signs in early dry eye. Curr Eye Res 2012; 37: 357–64.
15. Ergin A, Bozdogan O. Study on tear function abnormality in pterygium. Ophthalmologica 2001; 215: 204–8.
16. Julio G, Lluch S, Pujol P, Alonso S, Merindano D. Tear osmolarity and ocular changes in pterygium. Cornea 2012; 31: 1417–21.
17. Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res 2003; 76: 521–42.
18. Johnson ME, Murphy PJ. Measurement of ocular surface irritation on a linear interval scale with the ocular comfort index. Invest Ophthalmol Vis Sci 2007; 48: 4451–8.
19. Stern ME, Beuerman RW, Fox RI, Gao J, Mircheff AK, Pflugfelder SC. The pathology of dry eye: the interaction between the ocular surface and lacrimal glands. Cornea 1998; 17: 584–9.
20. Mathers WD, Nelson SE, Lane JL, Wilson ME, Allen RC, Folberg R. Confirmation of confocal microscopy diagnosis of Acanthamoeba
keratitis using polymerase chain reaction analysis. Arch Ophthalmol 2000; 118: 178–83.
21. Stern ME, Pflugfelder SC. Inflammation in dry eye. Ocul Surf 2004; 2: 124–30.
22. Tuominen IS, Konttinen YT, Vesaluoma MH, Moilanen JA, Helinto M, Tervo TM. Corneal innervation and morphology in primary Sjogren’s syndrome. Invest Ophthalmol Vis Sci 2003; 44: 2545–9.
23. Gilbard JP, Gray KL, Rossi SR. A proposed mechanism for increased tear-film osmolarity in contact lens wearers. Am J Ophthalmol 1986; 102: 505–7.
24. Villani E, Viola F, Sala R, Salvi M, Mapelli C, Curro N, Vannucchi G, Beck-Peccoz P, Ratiglia R. Corneal involvement in Graves’ orbitopathy: an in vivo
confocal study. Invest Ophthalmol Vis Sci 2010; 51: 4574–8.
25. Gallar J, Tervo TM, Neira W, Holopainen JM, Lamberg ME, Minana F, Acosta MC, Belmonte C. Selective changes in human corneal sensation associated with herpes simplex virus keratitis. Invest Ophthalmol Vis Sci 2010; 51: 4516–22.
26. Dushku N, John MK, Schultz GS, Reid TW. Pterygia pathogenesis: corneal invasion by matrix metalloproteinase expressing altered limbal epithelial basal cells. Arch Ophthalmol 2001; 119: 695–706.
27. Zander E, Weddell G. Observations on the innervations of the cornea. J Anat 1951; 85: 68–99.
28. Muller LJ, Vrensen GF, Pels L, Cardozo BN, Willekens B. Architecture of human corneal nerves. Invest Ophthalmol Vis Sci 1997; 38: 985–94.
29. Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res 2010; 90: 478–92.
30. Papadia M, Barabino S, Valente C, Rolando M. Anatomical and immunological changes of the cornea in patients with pterygium. Curr Eye Res 2008; 33: 429–34.
31. Wang Y, Zhao F, Zhu W, Xu J, Zheng T, Sun X. In vivo
confocal microscopic evaluation of morphologic changes and dendritic cell distribution in pterygium. Am J Ophthalmol 2010; 150: 650–5.
32. Stapleton F, Chui J, Tan M, Coroneo M. Effect of pterygium on corneal sensitivity (abstract). Clin Exp Ophthalmol 2002; 30 (Suppl.): A26.
33. Belmonte C, Gallar J. Cold thermoreceptors, unexpected players in tear production and ocular dryness sensations. Invest Ophthalmol Vis Sci 2011; 52: 3888–92.
34. Chui J, Di Girolamo N, Coroneo MT, Wakefield D. The role of substance P in the pathogenesis of pterygia. Invest Ophthalmol Vis Sci 2007; 48: 4482–9.
35. Belmonte C, Viana F. Transduction and encoding of noxious stimuli. In: Schmidt RF, Willis W, eds. Encyclopedia of Pain, Vol. 3. Berlin, Germany: Springer-Verlag; 2007: 2515–28.
36. Adatia FA, Michaeli-Cohen A, Naor J, Caffery B, Bookman A, Slomovic A. Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining in Sjogren’s syndrome. Can J Ophthalmol 2004; 39: 767–71.
Keywords:© 2013 American Academy of Optometry
pterygium; ocular discomfort; clinical morphology; corneal sensitivity; chronic inflammation